2012 -The Road Ahead for ME/CFS Pt. II: Rise of the Research Efforts

February 21, 2012

Posted by Cort Johnson

Background 

The biggest finding in CFS history (XMRV) didn’t work out and the most revered group in CFS history, the WPI, has troubles of its own, but ME/CFS research community emerged in better shape with more new projects and more new faces  than ever before. Yes, ME/CFS is still a fringe topic receiving abysmal funding from the federal government and these efforts are small, but they often lead by prominent researchers and if they are successful they should be able to pull in much needed funds over time.

In Part II of “The Road Ahead in 2012″ we  look forward to what we can expect from most of the ME/CFS research organizations in 2012.

CFIDS Association of America  http://www.research1st.com/

We’re intensifying efforts across the field to build a critical mass of rigorous researchthat validates the biological basis for CFS and leads to improved methods of diagnosis and treatment.

Research1st focuses on research into the cause of CFS

The CAA’s research program approach is different from other foundations founded by researchers to support their research. The CAA’s primary goal is to produce pilot studies that provide the data researchers need to apply for multi-million dollar grants from the NIH, Department of Defense (DOD) and other funding sources.

Instead of having in-house researchers do their research, CAA issues requests for grant proposals to broad research community and then puts the proposals through a rigorous and lengthy process (10 months) of analysis by independent reviewers (over 50) before the final projects are funded. An added bonus has been the presence of a veteran researcher at their helm, Dr. Suzanne Vernon, who love to roll up her sleeves and tweak, combine or otherwise alter original study proposals to make the whole package greater than its parts.

One result of this rather intensive approach is that CAA funded studies have paid off at the NIH with the CAA’s $1,000,000 plus 2009 investment resulting in over $5 million dollars in NIH/DOD grants and their researchers publishing 14 studies (with more on the way)

  • Research Grant Winners Announced – CAA announces the winners of their 2010 grant package on February 24th.
  • BioBank Expands – the CAA’s Biobank is the foundation of a potentially greatly expanded research effort as researchers apply for and use the CAA’s well-documented samples for their research studies. Thus far 449 patients and controls have enrolled and the Biobanks first study using 267 participants (on XMRV?) should be published this year. The Biobank will enroll more participants this year and hopefully will announce more collaborations.
  • From “Knowledgebase to Biomarker” – the CAA’s Goes Shopping – Mishra’s Knowledgebase study to create novel hypotheses using data mining techniques on over 250,000 (yes, that’s 250,000) articles on ME/CFS and 14 co-occurring disorders was one of the more unusual studies funded anywhere. That study is wrapping up this year and the CAA is going to begin shopping this new list of biomarker candidates to researchers and biotech companies in hopes they will start to validate them.
  • A Yea or Nay on the Autoimmune Study Decision Soon – Dr. Suzanne Vernon lead a host of researchers from across the US to apply for a grant to the Congressionally Directed Mandated Research Program (CDMRP) to study the possibility that ME/CFS has auto-immune characteristics. A Yea on the study would be opportune indeed given the results of the recent Rituximab trials. 


The Chronic Fatigue Initiative (CFI)
http://cfinitiative.org/  

We are focused on assembling the best team; developing a new strategy; formulating a straight-forward operating plan and driving results.

The Chronic Fatigue Initiative, with its 10 million dollar 3-year grant from the Hutchins Foundation, is the best funded ME/CFS non-profit research group in the world. Their hefty bank account means that the CFI has the bucks to fund large studies and with four ME/CFS doctors (Klimas, Peterson, Bateman, Montoya) providing 200 plus patients/200 healthy controls for they are.

A Busy Year – With the foundation of the Initiative – 400 rigorously described patients and healthy controls – ensconced in their Biobank – Foundation researchers can get down to work. The CFI will start off with two big studies.

  • Blood, Sweat, Tears and More – None is bigger than the big Hornig/Lipkin pathogen study, which, given its rigor and size, will probably define pathogen research in ME/CFS for quite some time. Hornig et. al. are using the latest technology, developed in Ian Lipkin’s lab, no less, to look for pathogens in the blood, as well as the saliva, tears and stool samples. Due date – late 2012, early 2013.
  • Size Matters – the Aschiero Epidemiology Study – Meanwhile Dr. Aschiero will be using a huge Harvard database and biobank to analyse samples which will hopefully tell what happened to make people come down with CFS.
  • Mechanisms of Illness – CFI will also be developing their scientific advisory board which will define likely “Mechanisms of Illness” , call for grants and then fund them. As with the CAA’s biobank the CFI’s biobank will be open to other researchers for use.

The word is that the Hutchins Family Foundation is willing to pump more money into the CFI if they feel their initial investment is paying off.

Fatigue Consultation Clinic and OFFER in Salt Lake City, Utah – Dr. Bateman

The mission of the Research Department is to develop the most effective treatments for fibromyalgia, ME/CFS, and associated illnesses through compliant partnerships with industry leaders and compassionate patient-centered research.

Fatigue Consultation Clinic – http://www.fcclinic.com/index.htm

  • Going Digital – “There’s gold in them hills”- there’s a trend going on In the top rank of ME/CFS physicians with Dr. Klimas, Dr. Peterson and Dr. Bateman all switching to Electronic Medical Records Systems to increase their productivity and allow them to better understand their data.
  • Collaboration, collaboration, collaboration – The Fatigue Consultation Clinic’s transition to an EMR/EHR, system will assist both their clinic and research arms and with Dr. Bateman engaged in collaborative efforts with the CFIDS Association of America, the Chronic Fatigue Initiative, the CDC and the Open Medicine Institute and the Lights at the University of Utah, this busy physician/researcher definitely doesn’t need to spend her time digging into her filing cabinets.
  • An Expansion - Dr. Bateman is in demand and the Fatigue Consultation Clinic has increased its space by 50%

OFFER (Organization for Fatigue and Fibromyalgia Education and Research) http://www.offerutah.org/index.htm

  • Professional Conference – Dr. Bateman’s non-profit , OFFER, is planning a continuing education conference for mental health providers regarding the science of chronic fatigue and pin in Sept. 2012.
  • The Long Term Goal – OFFER’s long term goal, still in its brainstorming stages, is establishing none other than a CFS/FM Center of Excellence in Salt Lake City ….and why not? Dr. Bateman is in demand, she has strong connections with Univ of Utah researchers (the Lights/Dr. Singh/ Dr. Albright), she is collaborating with virtually everyone and she is respected everywhere. Utah has become something of a hub of ME/CFS research.

Hunter-Hopkins Center – Dr. Lapp http://drlapp.com/

Dr. Lapp at the Hunter-Hopkins Center treats and researches CFSThe Hunter-Hopkins Center conducts clinical trials, nutraceutical trials, and clinical research. These studies are performed independently or collaboratively with other researchers throughout the world.

Lead by Dr. Lapp the Hunter Hopkins Center is always in the thick of treatment trials for ME/CFS and Fibromyalgia and this year is no exception. The HHC will be engaged in stud7ing

  • Ampligen – Like Dr. Enlander and Dr. Peterson, the Hunter-Hopkins Center is continuing to engage in Ampligen trials. 
  • IDEAL (Gamma Globulin) – gamma globulin is another understudied immuno-modulator and the HHC is working with Coram Services to gather data on patients given (Hyzentra ™ or Vivaglobin ™) subcutanteously. . This is part of a multivitamin-center national study.
  • Droxidopa – used in Japan with good effect in the treatment of low blood pressure and orthostatic intolerance, Droxidopa is just beginning to crack the US market. The HHC is finishing up a study to determine how effective it is in treating ME/CFS.
  • Physical findings in CFS/ME - “An ongoing study to identify significant physical findings in CFS/ME. We anticipate a multi-center, cross-specialty application of our findings in order to determine the incidence, sensitivity, and specificity of each finding.” (This may be the CDC/Open Medicine Institute sponsored trial)


Initiative for Chronic Infectious Diseases at Stanford – Dr. Montoya
http://chronicfatigue.stanford.edu/

Our initiative aims to mobilize and integrate Stanford’s best faculty and resources…  We have assembled a world-class research team, who will work to identify the connection between these patients’ symptoms and infection or immune dysfunction.

The past year has been rather quiet at Stanford as Dr. Montoya has been gathering his team of researchers, post-doctoral fellows, statisticians, bioinformatics faculty, graduate students, laboratory personnel (human immune monitoring core facility), a neuropsychologist, and an exercise physiologist. It appears that this year the Initiative for Chronic Infectious Diseases is going to make more noise.

The Year (?)  - Dr. Montoya’s eagerly awaited placebo controlled study using Valcyte was due to end five years ago. We know that the results were initially underwhelming yet interesting enough to keep this careful researcher engaged. In a talk a year or so ago, Dr. Kogelnik stated that most patients improved past the six month mark the study was due to end and some became well. That finding in this study would probably break things open for antivirals and ME/CFS….Here’s to the bet that this is the year Dr. Montoya reports on the big study.

The Initiative is engaged in a number of other studies including

  • The Lipkin pathogen study, an immune signatures study, an MRI brain study, and an EEG/exercise study to validate cognitive issues.
  • A new Website – the word is that a much improved website is almost upon us….as well :)

Lerner Foundation – Dr. Lerner 

http://www.treatmentcenterforcfs.com/CFS_Foundation/index.html

We have, along with a team of investigators at this Center, accumulated strong evidence that CFS is caused by persistent herpes virus infection (Epstein-Barr virus, Cytomegalovirus and Herpes virus 6), singly or in combination.

Dr. Lerner is excited (!) Now working with another EBV expert, Dr. Ron Glazer, Dr. Lerner believes he has found a ‘smoking gun’ which indicates that his theory of an ‘arrested’ Epstein Barr Virus infection in ME/CFS is correct. Their Ottawa IACFS/ME Conference poster indicated they’re picking up evidence of the early proteins he believes are present. The Glazer /Lerner study will continue and they will lobby the NIH for funding to develop an easier, less expensive Elisa test.
Neuro-immune Institute at Nova Southeastern (NSU)
in Broward Cty, Florida – Dr. Klimas

I can promise we will be providing cutting edge research and care, and educating providers like never before. 

Dr. Klimas has a lot on her plate after her move from the Univ of Miami to Nova Southeastern to form a Neuro-Immune Institute. Based on her statements thus far it sounds like she will be

  • Planning – Forming the Neuro-Immune Institutes long-range plan
  • Hiring 3 researchers – including at least one senior researcher
  • Fundraising – Taking part in a major fundraising effort
  • Developing web-based platforms to house their biological data
  • Collaborating – Developing onsite and virtual think tanks and collaborative opportunities
  • Educating – Developing educational opportunities at NSU
  • Research - including the Good/Bad Day study, systems biology research, NK cells research etc. 
  • CDC-  participating in the CDC diagnosis and definitions study

Dig Deeper – read “Dr Klimas Talks on her new CFS research Institute at Nova Southeastern 

Mt Sinai ME/CFS Research Center – Dr. Enlander

The advantage of being part of a large medical school which is supportive of  the ME /CFS center is that the range of experts and specialists is enormous, making the center a cohesive and important group with the largest cohort of ME/CFS patients  in the eastern seaboard.

The Mt Sinai ME/CFS research center is getting off to a great start with a big $1,000,000 grant and they have a long list of projects on the boards, four of which are already underway and a future project that will hopefully involve Rituximab.

  • Exercise and genes – a Pre and post-exertional genome study featuring ace geneticist Eric Schadt and Dr. Enlander.
  • Exercise and cytokines – this Enlander/Morad study will examine whether exercise tweaks cytokines and RNase L. Other studies have failed to find a strong link – will the Enlander/Morad study find differently? Hopefully we’ll know before long.
  • GcMAF and MAV 878 – an ongoing Enlander project to assess the effectiveness of the most exciting addition to the ME/CFS treatment package – GcMAF
  • Ampligen – ongoing Enlander/Hemispherx project with Dr. Enlander continues to assess the effectiveness of the immune modulator Ampligen

Projected projects include an Enlander/Bell Rituximab treatment trial and Ila Singh study on viruses.

PHANU (Population Health and Neuroimmunology Unit) – Dr. Marshall-Gradisnuk, Dr. Staines – http://www.bond.edu.au/faculties-colleges/faculty-of-health-sciences-and-medicine/research/research-groups-centres/population-health-and-neuroimmunology-unit/index.htm

Ultimately our aim is to develop a clear diagnostic test for CFS and establish a national testing facility here at Bond University, which we believe could happen within the next five years.”

PHANU, an ME/CFS research group at Bond University in Australia, is on the upswing. Their longstanding assertion that ME/CFS is an autoimmune disorder got a big boost with the Rituximab trial, they turned in the most impressive performance at the IACFS/ME Ottawa conference, and they just received an $800,000 grant from the Mason Foundation. They are working with Dr. Peterson of the Simmaron Foundation and looking to collaborate with others. Some of the studies they’re currently working on include

  • NK Cells – Tracking down the cause of Natural Killer Cell Dysfunction
  • Vaccinations – A window into the immune dysfunction in CFS?
  • Gene Expression during pregnancy in CFS
  • Immune Regulation and pain Sensitization in the central nervous system

PHANU will be determining how to spend their new grant money and they are working hard on getting a Rituximab study going. An interview with PHANU’s director, Dr. Marshall-Gradisnuk, is coming up shortly.

Simmaron Research Foundation – Dr Peterson- http://simmaronresearch.org/

We envision a future where CFS/ME is a treatable disease

One of the latest entrees to the ME/CFS research scene, Simmaron is building for the future. Their non-profit status is in, their Boards (of Directors, Scientific Advisory) are intact and they’re currently engaged in three studies

  • Lipkin XMRV study
  • Spinal fluid – an immunological spinal fluid study
  • Lipkin CFI pathogen study

On a side note Dr. Peterson is in the process of moving, after decades in his present office, to bigger and better digs.

Whittemore Peterson Institutehttp://wpinstitute.org/

The Whittemore Peterson Institute for Neuro-Immune Disease exists to bring discovery, knowledge, and effective treatments to patients with illnesses that are caused by dysregulation of both the immune and the nervous system.”

Dr’s Pourzan and Khaiboullina will anchor the WPI’ s treatment end and with the questions resolved about who gets the research money (the WPI/ Dr. Lombardi do), the WPI will be working on several large NIH and Dept. of Defense grants in 2012

  • New Strategies study…- the WPI is about halfway through a 5 year grant to uncover novel pathogens and immune markers. The Institute will use a variety of methods to look for novel pathogens and biomarkers. Among other things they will be using Kerr’s gene expression data that identified 88 dysregulated genes. This is a complex multi-million dollar study and the WPI is no doubt very glad they retained control of it.
  • Pathogenic Agents and Immune Markers Study – in this new 400K Dept. of Defense grant the WPI will look for pathogens and immune markers in Gulf War Illness (GWI) patients.

Events – The annual” I Hope You Dance” Gala will take place Sept 14 and Wings of Hope Run will take place Oct 14th.

Plus One More…

The appearance of S research efforts (Chronic Fatigue Initiative, CFI, Mt. Sinai, Neuroimmune Institute, Simmaron Researcj) and the growth of others (PHANU, CFIDS Association) has been gratifying but guess what? In the next month or two we’re due for one more ‘splash’. Stay tuned….

 

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3 comments

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Cort February 24, 2012 at 8:52 am

FDA Skeptical of Hypotension Drug
By John Gever, Senior Editor, MedPage Today
Published: February 22, 2012

http://www.medpagetoday.com/Neurolog…ink.net&mu_id=

An FDA staff review of droxidopa (Northera) for treating neurogenic orthostatic hypotension in patients with certain neurological diseases has recommended against its approval, according to documents released Tuesday.

The review, released in advance of a Thursday meeting of the agency’s Cardiovascular and Renal Drugs Advisory Committee, cited lack of evidence that droxidopa is effective for longer than four weeks and “worrisome safety signals” seen in clinical trials.

The latter included deaths, strokes, heart attacks, hypertensive crises, and underlying disease progression that occurred during the open-label phases of the trials.

Droxidopa is being developed by Chelsea Therapeutics for treating symptomatic, neurogenic orthostatic hypotension in patients with primary autonomic failure — which can be associated with Parkinson’s disease and multiple system atrophy — dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.

Currently, the only drug specifically approved for this indication is midodrine, and the FDA may soon pull it from the market because it has never been shown to be effective in rigorous trials.

Eight other drugs are used off-label, according to the FDA review, including indomethacin, desmopressin, and octeotide. Most have multiple contraindications and all have significant side effects, the review noted.

Droxidopa is a prodrug for norepinephrine, converted both peripherally and centrally as it crosses the blood-brain barrier. It therefore acts as a vasoconstrictor which, at least in theory, should help patients retain adequate blood pressure when they stand up from sitting or supine positions.

Chelsea’s marketing application is based on three safety-and-efficacy trials and two that examined only safety. A total of 535 patients were treated in the company’s clinical program, with only 341 receiving the drug for more than six weeks, the FDA reviewers noted.

Moreover, only 83 ever received the maximum dose of 600 mg three times a day.

As a result, the FDA staff review said, “the safety database of this development program was not robust.”

It also asserted that the available safety data were “not so clean.”

According to the review, “during the longer term open-label experience with droxidopa, there were several deaths, SAEs [serious adverse events], discontinuations for AEs, and events of hypertensive crisis, strokes, and myocardial infarction.”

Reviewers continued, “Of utmost concern are reports of neuroleptic malignant syndrome from Japan that aren’t clearly explained. During a 10-year reporting period, there were nine cases of neuroleptic malignant syndrome while patients were taking droxidopa.”

Although some of those cases could have arisen from other drugs patients were taking, there were several that “appeared to have no likely etiology” other than droxidopa exposure, the staff review indicated.

In addition, the reviewers questioned the study’s efficacy even in the short-term trial data. One of the two randomized trials failed to meet its primary endpoint, which was a statistically significant improvement in scores on the first item in the Orthostatic Hypotension Symptom Analysis scale.

But the review also noted points in the drug’s favor.

The other main study, also a randomized trial, documented improvements in hypotension symptoms of 0.9 and 1.3 points on two scales in which baseline scores were in the range of five to six, and which lasted at least one week. The same trial also showed that droxidopa increased standing systolic pressure for at least a week.

And, the trial that failed in its primary endpoint did show a significant benefit on a secondary efficacy endpoint, scores on the Orthostatic Hypotension Questionnaire.

The advisory committee will be asked to discuss the drug’s efficacy and safety record in the trial data, and will vote on whether it should be approved.

The FDA is not required to follow advisory committee recommendations, but it usually does.
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Victoria February 24, 2012 at 9:20 am

So much of this seems repetitive and certainly will be no help to the patient. You mention, for instance, Dr. Vernon looking for autoimmune links when that was already been proven way back in 2008 with thousands tested and you fail to mention the most exciting work on DNA by the National CFIDS Foundation collaborating with another charity.

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Cort February 25, 2012 at 11:04 am

Honestly I fail to see how uncovering possible blood vessel problems that inhibit blood flows to the brain, the most extensive pathogen study ever, the possibility that an endogenous retrovirus could be contributing to ME/CFS, etc. ”certainly will be no help to the patient”. I find that response baffling and ..yes, I missed the NCF (as well as Natelson’s group I was informed) but to discount everything else going on just doesn’t make sense to me. Lastly, I looked through the autoimmune literature on CFS earlier and found very little of it and much of it inconclusive – so I’m not sure what you’re referring to. I will look into the NCF’s work, however.

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